Irritable bowel syndrome (IBS) is a high prevalence disease, whose symptoms are reported by a large number of young adults with significant effects on quality of life and social costs. Traditionally, IBS has been treated with dietary and lifestyle modification, fiber supplementation, psychological and pharmacological therapy. Since its complex and multifactorial etiopathogenesis is only partially known, therapeutic choices may be difficult and not always effective. New research efforts focused on the role of relationship between central nervous system and gut disorders (brain-gut axis), altered composition of gut microbiota (e.g. an eight times increased risk for IBS after Salmonella infection), immune activation with an increased number of T lymphocytes and mast cells associated with mucosa as well as an increased level of pro-inflammatory cytokines (IL-10 and IL-12, suggesting Th1 polarization), visceral hypersensitivity causing perception of pain even for minimal abdominal distension. Based on these findings, new possibilities of treatment are emerging with encouraging outcomes. Attention is directed to drugs that showed good tolerability profile and poor systemic absorption, which may make them suitable for repeated or long term treatments, as frequently required in patients with IBS. They have been successfully used drugs such as tachykinin receptors antagonists, tryptophan hydroxylase inhibitors, bile acid sequestrants, µ agonist and δ antagonist opioid receptors. Recent studies are discussed in this review, focusing both on new therapeutic approaches and innovative adaptation of previously available treatments.